Ventrally emigrating neural tube cells migrate into the developing vestibulocochlear nerve and otic vesicle

Virtually all cell types in the inner ear develop from the cells of the otic vesicle. The otic vesicle is formed by the invagination of non-neural ectodermal cells known as the otic placode. We investigated whether a recently described cell population, originating from the ventral part of the hindbrain neural tube known as the ventrally emigrating neural tube (VENT) cells, also contributes cells to the otic vesicle. The ventral hindbrain neural tube cells were labeled with the fluorescent vital dye DiI or replication-deficient retroviruses containing the LacZ gene in chick embryos on embryonic day 2, after the emigration of neural crest from this region. One day later, the labeled cells were detected only in the hindbrain neural tube. Shortly thereafter, the labeled cells began to appear in the eighth (vestibulocochlear) cranial nerve and otic vesicle. From embryonic day 3.5-5, the labeled cells were detected in the major derivatives of the otic vesicle, i.e. the endolymphatic duct, semicircular canals, utricle, saccule, cochlea, and vestibulocochlear ganglion. That the emigrated cells originated from the ventral part of the hindbrain neural tube was confirmed by focal application of DiI impregnated filter paper and with quail chimeras. It is concluded that, in addition to the otic placode cells, the otic vesicle also contains the ventrally emigrating neural tube cells, and that both cell populations contribute to the structures and cell types in the inner ear. It is well known that inductive signals from the hindbrain are required for the morphogenesis of the inner ear. The migration of the hindbrain neural tube cells into the otic vesicle raises the possibility that the inductive effect of the hindbrain might be mediated, at least in part, by the ventrally emigrating neural tube cells and that, therefore, a mechanism exists that involves cells rather than diffusible molecules only.     

In vivo biological validation and biophysical modeling of the sensitivity and positive accuracy of endocrine peak detection. II. The follicle-stimulating hormone pulse signal

Despite interest in the in vivo control of gonadotropin release, valid assessment of the physiological regulation of the pulsatile secretion of the gonadotropin FSH has been hampered by the uncertain validity and reliability of available FSH peak detection algorithms. Difficulties in identifying FSH peaks accurately are believed to arise in part because of the slow metabolic clearance of this glycoprotein hormone. Here, we have used two complementary strategies to test the validity of FSH pulse detection. First, by means of a computer-assisted mathematical model for simulating episodic hormone secretion, we evaluated the effects of various putative FSH secretory pulse amplitudes and half-lives on the sensitivity and positive accuracy of peak detection. Secondly, we used an in vivo primate animal model, in which presumptively true FSH pulses were evaluated independently by continuous electrophysiological monitoring of mediobasal hypothalamic multiunit activity. These two approaches allowed us to define optimal pulse analysis parameters that yield maximal sensitivity and positive accuracy for detecting FSH peaks in synthetic and biological time series. We found (as predicted intuitively) that increasing half-times of hormone disappearance decrease both the sensitivity and positive accuracy of peak detection for any given peak detection thresholds and hormone secretory amplitudes. However, adequately sampled episodic FSH time series could be analyzed for FSH pulsatility by an appropriately constrained, objective computerized algorithm with reasonable (less than 10-15%) false negative and false positive errors, such that resultant sensitivity and positive accuracy exceed 85-90%. Of interest, computer simulations and the in vivo animal model exhibited similar discriminative capabilities. We conclude that increasing half-times of hormone (e.g. FSH) removal do impair hormone peak detection sensitivity and positive accuracy. Nevertheless, gonadotropin time series can be analyzed for FSH pulsatility in a valid manner with adequately constrained false negative and false positive error rates.     

Aetiology of neonatal septicaemia in Qatif, Saudi Arabia

Neonatal septicaemia (NNS) is a major cause of neonatal morbidity and mortality. Neonatal septicaemia was studied to determine the incidence, common bacterial aetiology and antibiotic susceptibility in Qatif Central Hospital, Saudi Arabia. Of 1,797 babies admitted into the unit over a 3 year period, 144 (8.0%) had documented neonatal septicaemia consisting of 94 (65%) late onset and 50 (35%) early onset septicaemia. The incidence was 8.2/1000 of the total live births in the hospital.

Gram negative bacteria were encountered in 66.2%, gram positive bacteria in 29.2% and Candida albicans in 4.4% of the case. Klebsiella spp., E. coli, and Pseudomonas accounted for 81.8 % of the gram negative while Staphylococcus epidermidis, Staphylococcus aureus and group B Beta haemolytic Streptococcus accounted for 73.9% of the gram positive bacteria.

Most of Gram negative bacteria had a high sensitivity to Aminoglycosides and third generation Cephalosporins. Coagulase negative staphylococci were frequently resistant to most antibiotics but always sensitive to Vancomycin. The overall mortality rate was 18.7%.     

Antitumor xenograft activity with a conjugate of a Vinca derivative and the squamous carcinoma-reactive monoclonal antibody PF1/D

The human squamous carcinoma-reactive murine monoclonal antibody PF1/D was used to derive a conjugate with the Vinca derivative 4-desacetylvinblastine-3-carboxyhydrazide (PF1/D-DAVLBHYD). This immunoconjugate was shown to be largely aggregate free and there was no loss of immunoreactivity postconjugation. When tested in vivo in a 3-day-established human squamous carcinoma nude mouse xenograft model, the PF1/D-DAVLBHYD conjugate eliminated tumor growth with three injections (days 3, 6, and 9) at 2 mg/kg Vinca content. Significant tumor suppression was also observed with 0.5 mg/kg conjugate doses. In contrast, free PF1/D antibody had minimal antitumor activity and no activity was seen with identical doses of a control non-tumor-binding IgG-DAVLBHYD conjugate. Together, these data demonstrate the specificity of the PF1/D-DAVLBHYD antitumor effects.     

Initial two-year results of the Oregon Liver Transplantation Program

During the first 24 months of the Oregon Liver Transplantation Program, which began in October 1988, 94 patients were formally evaluated and 47 adults underwent 54 liver transplantations. Thirty-four percent of patients were veterans. The recipient operation lasted a mean of 7.4 hours (range: 4 to 16 hours). Veno-venous bypass was used routinely at first but selectively later (7 of the last 26 cases), resulting in reduced operating time. Hepatic artery reconstruction was end-to-end anastomosis in 52 cases and iliac conduit in 2. No arterial thrombosis occurred. Biliary reconstruction was choledochocholedochostomy in 83% and choledochojejunostomy in 17%. Biliary complications occurred in 28%. Operative mortality was 2%, and 1-year actual survival was 80%. Patients with hepatitis B fared worse, with four of six dying at a mean of 7.6 months. Overall, the median hospital stay was 30 days. Patients surviving more than 3 months had a mean Karnofsky score of 82%. No significant difference in outcome was noted in patients receiving prophylactic OKT3 monoclonal antibody (used in 45%) versus conventional immunosuppressive therapy. Overall, allograft rejection occurred in 55% of patients. Retransplantation was required in seven patients, three for primary graft nonfunction, two for uncontrolled rejection during induction therapy with OKT3, and two for graft failure secondary to recurrent hepatitis B.